Melphalan-associated pulmonary toxicity following high-dose therapy with autologous hematopoietic stem cell transplantation

Abstract

Summary:Melphalan can rarely cause interstitial pneumonitis and fibrosis. Although it has been reported previously in patients after conventional doses, we report four cases developing diffuse interstitial pneumonitis (DIP) after high-dose melphalan-based therapy. In a 3-year period, four of 57 (7%) consecutive patients undergoing highdose melphalan (200 mg/m 2 ; MEL 200) were identified with DIP. Two patients who were heavily pre-treated with alkylators developed progressive respiratory failure despite high-dose steroids and eventually died. The other two patients previously treated with vincristine, adriamycin, and dexamethasone (VAD) improved dramatically on high-dose steroids with complete resolution of their pneumonitis. Melphalan should be added to the growing list of alkylators causing pulmonary toxicity.

Treosulfan-based conditioning before hematopoietic SCT: more than a BU look-alike

“…Pneumonitis and pulmonary toxicity, 51,[56][57][58] or severe left ventricular failure/cardiac toxicity, 56,59 that was previously reported with fludarabine and reduced-dose BU or melphalan combinations were not observed with Treosulfan.…”

Treosulfan and fludarabine: a new toxicity-reduced conditioning regimen for allogeneic hematopoietic stem cell transplantation

“…No VOD occurred in the patients treated with treosulfan and fludarabine. Pneumonitis and pulmonary toxicity [33][34][35][36] or severe left ventricular failure/cardiac toxicity 6,34 associated with reduced-dose busulfan and fludarabine or melphalan combinations was likewise not observed. The treatmentrelated mortality was not a consequence of nonhematologic side effects of the conditioning regimen but resulted in 4 of the 6 cases from infections associated with direct immunosuppression or GVHD.…”

Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience

“…17,18 There was no cardiac toxicity, which can occur with melphalan, and no pulmonary fibrosis, which can be a complication of the use of busulfan. [19][20][21] Twelve of 44 patients (27%) transplanted at age younger than 1 year and 5 of 26 (19%) at age more than 1 year required admission to an intensive care unit. As a comparison, 146 patients undergoing fludarabine with melphalan conditioning largely for PID have recently been analyzed (Rao et al, manuscript in preparation): although the survival (76%) of those transplanted aged less than 1 year was similar to that of the rest of the group, the incidence of serious events needing intensive care support was higher in this group: 17 of 30 patients (57%) needed intensive care management.…”